US2021253589A1PendingUtilityA1
Aminomethylamidine and methylamidine antimicrobial compounds
Est. expiryJun 6, 2038(~11.9 yrs left)· nominal 20-yr term from priority
Inventors:Ashoke BhattacharjeeSomenath ChowdhuryErin M. DuffyJoseph A. IppolitoZoltan F. KanyoWan LauYuanqing TangYusheng Wu
A61P 31/04C07D 487/04C07D 487/14
43
PatentIndex Score
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Claims
Abstract
The present disclosure relates generally to the field of antimicrobial compounds and to methods of making and using them. In some embodiments, the present disclosure provides pyrrolo[2,3-d]pyrimidin-2-ones useful for treating, preventing, reducing the risk of, and delaying the onset of microbial infections in humans and animals.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula (I):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer,
wherein:
R 1 is selected from H and halo;
R 2 is selected from H and halo;
R 3 is selected from H, C 1-6 alkyl, and C 3-6 cycloalkyl;
R 4 is selected from H and halo;
R 5 is H;
R 6 is selected from H, C 2-6 alkenyl, and (C 1-4 alkyl)R A ;
R A is selected from H, NHR B , C(═O)R C , S(C 1-4 alkyl), C 3-6 cycloalkyl, and C 3-6 heterocycloalkyl ring containing 1 or 2 heteroatoms selected from N and O;
R B is selected from H, S(O) 2 (C 1-4 alkyl), and C(═O)C 1-4 alkyl;
R C is selected from NH 2 and OH; or
R 5 and R 6 together with the atoms to which they are attached form a 7-membered heterocyclic ring fused to the phenyl ring substituted with R 4 :
R 7 is H;
R 8A is H; or
R 7 and R 8A together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms forms a ring selected from the formulae:
R 8B is selected from H and C 1-6 alkyl;
R 9 is H;
R 10 is C 1-4 alkyl optionally substituted with an amino group; or
R 9 and R 10 together with the atoms to which they are attached form a ring of the formula:
and
n is 0 or 1;
with the proviso that the compound is not a compound selected from:
2 . The compound of claim 1 , wherein R 1 is selected from H and fluoro.
3 . The compound of claim 1 , wherein R 1 is fluoro.
4 . The compound of any one of claims 1 - 3 , wherein R 2 is selected from H and chloro.
5 . The compound of any one of claims 1 - 3 , wherein R 2 is chloro.
6 . The compound of claim 1 , wherein R 1 is fluoro and R 2 is chloro.
7 . The compound of any one of claims 1 - 6 , wherein R 3 is selected from C 1-6 alkyl and C 1-6 cycloalkyl.
8 . The compound of any one of claims 1 - 6 , wherein R 3 is C 1-3 alkyl.
9 . The compound of any one of claims 1 - 6 , wherein R 3 is methyl.
10 . The compound of any one of claims 1 - 6 , wherein R 3 is C 1-6 cycloalkyl.
11 . The compound of any one of claims 1 - 6 , wherein R 3 is cyclopropyl.
12 . The compound of any one of claims 1 - 11 , wherein R 4 is selected from H and fluoro.
13 . The compound of any one of claims 1 - 11 , wherein R 4 is H.
14 . The compound of any one of claims 1 - 11 , wherein R 4 is fluoro.
15 . The compound of any one of claims 1 - 14 , wherein R 5 is H.
16 . The compound of any one of claims 1 - 15 , wherein R 7 is H.
17 . The compound of any one of claims 1 - 16 , wherein R 8A is H.
18 . The compound of any one of claims 1 - 15 , wherein R 7 and R 8A form a ring selected from the formulae:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 .
19 . The compound of any one of claims 1 - 18 , wherein R 6 is selected from H, C 2-4 alkenyl, and (C 1-2 alkyl)R A .
20 . The compound of any one of claims 1 - 19 , wherein R 6 is H.
21 . The compound of any one of claims 1 - 19 , wherein R 6 is propenyl.
22 . The compound of any one of claims 1 - 19 , wherein R 6 is CH 2 R A .
23 . The compound of any one of claims 1 - 19 , wherein R 6 is CH 2 CH 2 R A .
24 . The compound of any one of claims 1 - 19 , 22 , and 23 , wherein R A is NHR B .
25 . The compound of claim 24 , wherein R B is H.
26 . The compound of claim 24 , wherein R B is S(O) 2 CH 3 .
27 . The compound of claim 24 , wherein R B is C(═O)CH 3 .
28 . The compound of any one of claims 1 - 19 , 22 , and 23 , wherein R A is C(═O)R C .
29 . The compound of claim 28 , wherein R C is NH 2 .
30 . The compound of claim 28 , wherein R C is OH.
31 . The compound of any one of claims 1 - 19 , 22 , and 23 , wherein R A is S(CH 3 ).
32 . The compound of any one of claims 1 - 19 , 22 , and 23 , wherein R A is cyclopropyl.
33 . The compound of any one of claims 1 - 19 , 22 , and 23 , wherein R A is a ring selected from the formulae:
34 . The compound of any one of claims 1 - 15 , wherein R 7 and R 8A form a ring of the formula:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 .
35 . The compound of any one of claims 1 - 17 , wherein R 5 and R 6 together with the atoms to which they are attached form a 7-membered heterocyclic ring fused to the phenyl ring substituted with R 4 :
36 . The compound of any one of claims 1 - 35 , wherein R 8B is selected from H and C 1-3 alkyl.
37 . The compound of any one of claims 1 - 35 , wherein R 8B is H.
38 . The compound of any one of claims 1 - 35 , wherein R 8B is methyl.
39 . The compound of any one of claims 1 - 38 , wherein R 9 is H.
40 . The compound of any one of claims 1 - 39 , wherein R 10 is C 1-4 alkyl optionally substituted with an amino group.
41 . The compound of any one of claims 1 - 39 , wherein R 10 is methyl.
42 . The compound of any one of claims 1 - 39 , wherein R 10 is CH 2 NH 2 .
43 . The compound of any one of claims 1 - 38 , wherein R 9 and R 10 together with the atoms to which they are attached form a ring of the formula:
44 . The compound of any one of claims 1 - 43 , wherein n is 0.
45 . The compound of any one of claims 1 - 43 , wherein n is 1.
46 . The compound of claim 1 , wherein:
R 1 is halo; R 2 is halo; R 3 is selected from C 1-6 alkyl and C 1-6 cycloalkyl; R 4 is H; R 5 and R 6 together with the atoms to which they are attached form a 7-membered heterocyclic ring fused to the phenyl ring substituted with R 4 :
R 7 is H;
R 8A and R 8B are H;
R 9 is H;
R 10 is C 1-4 alkyl optionally substituted with an amino group; and
n is 1.
47 . The compound of claim 1 , wherein:
R 1 is halo; R 2 is halo; R 3 is C 1-6 alkyl; R 4 is selected from H and halo; R 5 is H; R 6 is selected from H, C 2-6 alkenyl, and (C 1-4 alkyl)R A ; R A is selected from NHR B , C(═O)R C , S(C 1-4 alkyl), C 3-6 cycloalkyl, and C 3-6 heterocycloalkyl ring containing 1 or 2 heteroatoms selected from N and O; R B is selected from H, S(O) 2 (C 1-4 alkyl), and C(═O)C 1-4 alkyl; R C is selected from NH 2 and OH; R 7 and R 8A form a ring of the formula:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 ;
R 9 is H;
R 10 is C 1-4 alkyl; and
n is 1.
48 . The method of claim 1 , wherein:
R 1 is halo; R 2 is halo; R 3 is C 1-6 alkyl; R 4 is H; R 5 is H; R 7 and R 8A form a ring of the formula:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 ;
R 9 and R 10 form a ring of the formula:
and
n is 0 or 1.
49 . The compound of claim 1 , wherein:
R 1 is halo; R 2 is halo; R 3 is selected from C 1-6 alkyl and C 1-6 cycloalkyl; R 4 is H; R 5 is H; R 7 and R 8A form a ring of the formula:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 ;
R 8B is selected from H and C 1-6 alkyl;
R 9 is H;
R 10 is C 1-4 alkyl optionally substituted with an amino group; and
n is 1.
50 . The compound of claim 1 , wherein:
R 1 is halo; R 2 is halo; R 3 is C 1-6 alkyl; R 4 is H; R 5 is H; R 7 and R 8A form a ring of the formula:
R 9 is H;
R 10 is C 1-4 alkyl optionally substituted with an amino group; and
n is 1.
51 . The compound of claim 50 , wherein R 7 and R 8A form a ring selected from the formulae:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 .
52 . The compound of claim 1 , wherein:
R 1 is halo; R 2 is halo; R 3 is C 1-6 alkyl; R 4 is H; R 5 is H; R 7 and R 8A form a ring of the formula:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 ;
R 9 is H;
R 10 is C 1-4 alkyl; and
n is 1.
53 . The compound of claim 1 , wherein the compound of Formula (I) has the Formula (Ia):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer.
54 . The compound of claim 1 , wherein the compound of Formula (I) has a formula selected from Formulae (Ib)-(Ih):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer.
55 . The compound of claim 1 , wherein the compound of Formula (I) is selected from:
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer.
56 . The compound of claim 1 , wherein the compound of Formula (I) is selected from:
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer.
57 . A compound of Formula (II):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer,
wherein:
R 1 is selected from H and halo;
R 2 is selected from H and halo;
R 3 is selected from H, C 1-6 alkyl, and C 3-6 cycloalkyl;
R 5 is H;
R 6 is selected from H, C 2-6 alkenyl, and (C 1-4 alkyl)R A ;
R A is selected from H, NHR B , C(═O)R C , S(C 1-4 alkyl), C 3-6 cycloalkyl, and C 3-6 heterocycloalkyl ring containing 1 or 2 heteroatoms selected from N and O;
R B is selected from H, S(O) 2 (C 1-4 alkyl), and C(═O)C 1-4 alkyl;
R C is selected from NH 2 and OH; or
R 5 and R 6 together with the atoms to which they are attached form a 7-membered heterocyclic ring fused to the phenyl ring substituted with R 4 :
R 7 is H;
R 8A is H; or
R 7 and R 8A together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms forms a ring selected from the formulae:
R 8B is selected from H and C 1-6 alkyl;
R 9 is H;
R 10 is C 1-4 alkyl optionally substituted with an amino group; or
R 9 and R 10 together with the atoms to which they are attached form a ring of the formula:
and
n is 0 or 1,
with the proviso that the compound is not a compound selected from:
58 . The compound of claim 57 , wherein R 1 and R 2 are each independently selected from H, chloro, and fluoro.
59 . The compound of claim 58 , wherein R 1 is fluoro and R 2 is chloro.
60 . The compound of any one of claims 57 - 59 , wherein R 3 is selected from C 1-6 alkyl and C 1-6 cycloalkyl.
61 . The compound of claim 60 , wherein R 3 is methyl.
62 . The compound of claim 60 , wherein R 3 is cyclopropyl.
63 . The compound of any one of claims 57 - 62 , wherein R 7 and R 8A form a ring selected from the formulae:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 .
64 . The compound of any one of claims 57 - 63 , wherein R 6 is selected from H, C 2-4 alkenyl, and (C 1-2 alkyl)R A .
65 . The compound of any one of claims 57 - 64 , wherein R 6 is propenyl.
66 . The compound of any one of claims 57 - 64 , wherein R A is NHR B .
67 . The compound of claim 66 , wherein R B is H.
68 . The compound of claim 66 , wherein R B is S(O) 2 CH 3 .
69 . The compound of claim 66 , wherein R B is C(═O)CH 3 .
70 . The compound of any one of claims 57 - 64 , wherein R A is C(═O)R C .
71 . The compound of claim 70 , wherein R C is NH 2 .
72 . The compound of claim 70 , wherein R C is OH.
73 . The compound of any one of claims 57 - 64 , wherein R A is S(CH 3 ).
74 . The compound of any one of claims 57 - 64 , wherein R A is cyclopropyl.
75 . The compound of any one of claims 57 - 64 , wherein R A is a ring selected from the formulae:
76 . The compound of any one of claims 57 - 75 , wherein R 8B is H.
77 . The compound of any one of claims 57 - 75 , wherein R 8B is methyl.
78 . The compound of any one of claims 57 - 77 , wherein R 8B is C 1-4 alkyl optionally substituted with an amino group.
79 . The compound of any one of claims 57 - 77 , wherein R 10 is methyl.
80 . The compound of any one of claims 57 - 77 , wherein R 10 is CH 2 NH 2 .
81 . The compound of any one of claims 57 - 77 , wherein R 9 and R 10 together with the atoms to which they are attached form a ring of the formula:
82 . A compound of Formula (III):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer,
wherein:
R 1 is selected from H and halo;
R 2 is selected from H and halo;
R 3 is selected from H, C 1-6 alkyl, and C 3-6 cycloalkyl;
R 4 is selected from H and halo;
R 5 is H;
R 9 is H;
R 10 is C 1-4 alkyl optionally substituted with an amino group; or
R 9 and R 10 together with the atoms to which they are attached form a ring of the formula:
and
n is 0 or 1,
with the proviso that the compound is not a compound selected from:
83 . The compound of claim 82 , wherein R 1 is fluoro and R 2 is chloro.
84 . The compound of claim 82 or claim 83 , wherein R 3 is methyl.
85 . The compound of any one of claims 82 - 84 , wherein R 4 is selected from H and fluoro.
86 . The compound of claim 85 , wherein R 4 is H.
87 . The compound of any one of claims 82 - 86 , wherein R 5 is H.
88 . The compound of any one of claims 82 - 87 , wherein R 9 and R 10 together with the atoms to which they are attached form a ring of the formula:
89 . The compound of any one of claims 82 - 88 , wherein n is 0.
90 . The compound of any one of claims 82 - 88 , wherein n is 1.
91 . A compound of Formula (IV):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer,
wherein:
R 1 is selected from H and halo;
R 2 is selected from H and halo;
R 3 is selected from H, C 1-6 alkyl, and C 3-6 cycloalkyl;
R 4 is selected from H and halo;
R 5 is H;
R 6 is selected from C 2-6 alkenyl and (C 1-4 alkyl)R A ;
R A is selected from H, NHR B , C(═O)R C , S(C 1-4 alkyl), C 3-6 cycloalkyl, and C 3-6 heterocycloalkyl ring containing 1 or 2 heteroatoms selected from N and O;
R B is selected from H, S(O) 2 (C 1-4 alkyl), and C(═O)C 1-4 alkyl;
R C is selected from NH 2 and OH;
R 9 is H;
R 10 is C 1-4 alkyl optionally substituted with an amino group; or
R 9 and R 10 together with the atoms to which they are attached form a ring of the formula:
and
n is 0 or 1,
with the proviso that the compound is not a compound selected from:
92 . The compound of claim 91 , wherein R 1 is fluoro and R 2 is chloro.
93 . The compound of claim 91 or claim 92 , wherein R 3 is methyl.
94 . The compound of any one of claims 91 - 93 , wherein R 4 is H.
95 . The compound of any one of claims 91 - 94 , wherein R 6 is propenyl.
96 . The compound of any one of claims 91 - 94 , wherein R 6 is selected from CH 2 R A and CH 2 CH 2 R A .
97 . The compound of any one of claims 91 - 94 and 96 , wherein R A is NHR B .
98 . The compound of claim 97 , wherein R B is H.
99 . The compound of claim 97 , wherein R B is S(O) 2 CH 3 .
100 . The compound of claim 97 , wherein R B is C(═O)CH 3 .
101 . The compound of any one of claims 91 - 94 and 96 , wherein R A is C(═O)R C .
102 . The compound of claim 101 , wherein R C is NH 2 .
103 . The compound of claim 101 , wherein R C is OH.
104 . The compound of any one of claims 91 - 94 and 96 , wherein R A is S(CH 3 ).
105 . The compound of claim 104 , wherein R A is cyclopropyl.
106 . The compound of claim 104 , wherein R A is a ring selected from the formulae:
107 . The compound of any one of claims 91 - 106 , wherein R 10 is methyl.
108 . The compound of any one of claims 91 - 107 , wherein n is 1.
109 . A compound of Formula (V):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer,
wherein:
R 1 is halo;
R 2 is halo;
R 3 is selected from C 1-6 alkyl and C 3-6 cycloalkyl;
R 10 is C 1-4 alkyl optionally substituted with an amino group; and
R 8A is H; R 8B is H; and R 5 and R 6 together with the atoms to which they are attached form a 7-membered heterocyclic ring fused to the adjacent phenyl ring:
or
R 5 is H; and R 7 and R 8A together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms forms a ring selected from the formulae:
110 . The compound of claim 109 , wherein R 1 and R 2 are each independently selected from H, chloro, and fluoro.
111 . The compound of claim 110 , wherein R 1 is fluoro and R 2 is chloro.
112 . The compound of any one of claims 109 - 111 , wherein R 3 is selected from C 1-6 alkyl and C 1-6 cycloalkyl.
113 . The compound of claim 112 , wherein R 3 is C 1-3 alkyl.
114 . The compound of claim 113 , wherein R 3 is methyl.
115 . The compound of claim 112 , wherein R 3 is C 1-6 cycloalkyl.
116 . The compound of claim 115 , wherein R 3 is cyclopropyl.
117 . The compound of any one of claims 109 - 116 , wherein R 8A is H; R 8B is H; and R 5 and R 6 together with the atoms to which they are attached form a 7-membered heterocyclic ring fused to the adjacent phenyl ring:
118 . The compound of any one of claims 109 - 116 , wherein R 5 is H; and R 7 and R 8A form a ring selected from the formulae:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 5 .
119 . The compound of claim 118 , wherein R 7 and R 8A form a ring of the formula:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 5 .
120 . The compound of claim 118 , wherein R 7 and R 8A form a ring of the formula:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 5 .
121 . The compound of claim 118 , wherein R 7 and R 8A form a ring of the formula:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 5 .
122 . The compound of any one of claims 109 - 121 , wherein R 10 is C 1-4 alkyl optionally substituted with an amino group.
123 . The compound of claim 122 , wherein R 10 is methyl.
124 . The compound of claim 122 , wherein R 10 is CH 2 NH 2 .
125 . The compound of claim 109 , wherein the compound of Formula (V) is selected from:
126 . The compound of claim 109 , wherein the compound of Formula (V) is selected from:
127 . A compound of Formula (VI):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer,
wherein:
R 1 is selected from H and halo;
R 2 is selected from H and halo;
R 3 is selected from H, C 1-6 alkyl, and C 3-6 cycloalkyl;
R 4 is selected from H and halo;
R 5 is H;
R 6 is selected from H, C 2-6 alkenyl, and (C 1-4 alkyl)R A ;
R A is selected from H, NHR B , C(═O)R C , S(C 1-4 alkyl), C 3-6 cycloalkyl, and C 3-6 heterocycloalkyl ring containing 1 or 2 heteroatoms selected from N and O;
R B is selected from H, S(O) 2 (C 1-4 alkyl), and C(═O)C 1-4 alkyl;
R C is selected from NH 2 and OH; or
R 5 and R 6 together with the atoms to which they are attached form a 7-membered heterocyclic ring fused to the phenyl ring substituted with R 4 :
R 7 is H;
R 8A is H; or
R 7 and R 8A together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms forms a ring selected from the formulae:
R 8B is selected from H and C 1-6 alkyl; and
n is 0 or 1.
128 . The compound of claim 127 , wherein R 1 and R 2 are each independently selected from H, chloro, and fluoro.
129 . The compound of claim 128 , wherein R 1 is fluoro and R 2 is chloro.
130 . The compound of any one of claims 127 - 129 , wherein R 3 is C 1-3 alkyl.
131 . The compound of claim 130 , wherein R 3 is methyl.
132 . The compound of any one of claims 127 - 131 , wherein R 4 is H.
133 . The compound of any one of claims 127 - 132 , wherein R 5 is H.
134 . The compound of any one of claims 127 - 133 , wherein R 7 and R 8A form a ring selected from the formulae:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 .
135 . The compound of any one of claims 127 - 134 , wherein R 6 is H.
136 . The compound of any one of claims 127 - 133 , wherein R 7 and R 8A form a ring of the formula:
wherein the * indicates the ring carbon that is attached to the phenyl ring substituted with R 4 and R 5 .
137 . The compound of any one of claims 127 - 136 , wherein n is 0.
138 . The compound of any one of claims 127 - 136 , wherein n is 1.
139 . The compound of claim 127 , wherein the compound of Formula (VI) is selected from:
140 . The compound of claim 127 , wherein the compound of Formula (VI) is selected from:
141 . A compound of Formula (VII):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer,
wherein:
R 1 is selected from H and halo;
R 2 is selected from H and halo;
R 3 is selected from H, C 1-6 alkyl, and C 3-6 cycloalkyl;
R 6 is selected from C 2-6 alkenyl, and (C 1-4 alkyl)R A ;
R A is selected from NHR B , C(═O)R C , S(C 1-4 alkyl), C 3-6 cycloalkyl, and C 3-6 heterocycloalkyl ring containing 1 or 2 heteroatoms selected from N and O;
R B is selected from H, S(O) 2 (C 1-4 alkyl), and C(═O)C 1-4 alkyl; and
R C is selected from NH 2 and OH.
142 . The compound of claim 141 , wherein R 1 and R 2 are each independently selected from H, chloro, and fluoro.
143 . The compound of claim 142 , wherein R 1 is fluoro and R 2 is chloro.
144 . The compound of any one of claims 141 - 143 , wherein R 3 is C 1-3 alkyl.
145 . The compound of claim 144 , wherein R 3 is methyl.
146 . The compound of any one of claims 141 - 145 , wherein R 6 is selected from C 2-4 alkenyl and (C 1-2 alkyl)R A .
147 . The compound of any one of claims 141 - 146 , wherein R 6 is propenyl.
148 . The compound of any one of claims 141 - 146 , wherein R 6 is CH 2 R A .
149 . The compound of any one of claims 141 - 146 , wherein R 6 is CH 2 CH 2 R A .
150 . The compound of any one of claims 141 - 146 , 148 , and 149 , wherein R A is NHR B .
151 . The compound of claim 150 , wherein R B is H.
152 . The compound of claim 150 , wherein R B is S(O) 2 CH 3 .
153 . The compound of claim 150 , wherein R B is C(═O)CH 3 .
154 . The compound of any one of claims 141 - 146 , 148 , and 149 , wherein R A is C(═O)R C .
155 . The compound of claim 154 , wherein R C is NH 2 .
156 . The compound of claim 154 , wherein R C is OH.
157 . The compound of any one of claims 141 - 146 , 148 , and 149 , wherein R A is S(CH 3 ).
158 . The compound of any one of claims 141 - 146 , 148 , and 149 , wherein R A is cyclopropyl.
159 . The compound of any one of claims 141 - 146 , 148 , and 149 , wherein R A is a ring selected from the formulae:
160 . The compound of claim 141 , wherein the compound of Formula (VII) is selected from:
161 . The compound of claim 141 , wherein the compound of Formula (VII) is selected from:
162 . A compound of Formula (VIII):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer,
wherein:
R 1 is selected from H and halo;
R 2 is selected from H and halo;
R 3 is selected from H, C 1-6 alkyl, and C 3-6 cycloalkyl;
R 4 is selected from H and halo; and
R 10 is C 1-4 alkyl optionally substituted with an amino group.
163 . The compound of claim 162 , wherein R 1 and R 2 are each independently selected from H, chloro, and fluoro.
164 . The compound of claim 163 , wherein R 1 is fluoro and R 2 is chloro.
165 . The compound of any one of claims 162 - 164 , wherein R 3 is selected from C 1-6 alkyl and C 1-6 cycloalkyl.
166 . The compound of claim 165 , wherein R 3 is C 1-3 alkyl.
167 . The compound of claim 166 , wherein R 3 is methyl.
168 . The compound of claim 165 , wherein R 3 is C 1-6 cycloalkyl.
169 . The compound of claim 168 , wherein R 3 is cyclopropyl.
170 . The compound of any one of claims 162 - 169 , wherein R 4 is H.
171 . The compound of any one of claims 162 - 170 , wherein R 10 is C 1-4 alkyl optionally substituted with an amino group.
172 . The compound of claim 171 , wherein R 10 is methyl.
173 . The compound of claim 171 , wherein R 10 is CH 2 NH 2 .
174 . The compound of claim 162 , wherein the compound of Formula (VIII) is:
175 . The compound of claim 1 , wherein the compound of Formula (VIII) is:
176 . A pharmaceutical composition comprising a compound of any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, and a pharmaceutically acceptable carrier.
177 . A method of treating, preventing, reducing the risk of, or delaying the onset of microbial infection, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, or a pharmaceutically acceptable composition of claim 176 .
178 . A method of treating, preventing, reducing the risk of, or delaying the onset of a microbial infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, or a pharmaceutically acceptable composition of claim 176 , wherein the infection is caused by or involves one or more microorganisms which are capable of being used as biological weapons, or the infection is caused by or involves one or more microorganisms which are extremely-drug resistant Gram-positive or Gram-negative pathogens.
179 . The method of claim 178 , wherein the one or more microorganisms are selected from the group consisting of biodefense category A pathogens Bacillus anthracis (anthrax), Yersinia pestis (plague), and Francisella tularensis (tularemia).
180 . The method of claim 178 , wherein the one or more microorganisms are selected from the group consisting of biodefense category B pathogens Burkholderia pseudomallei (melioidosis), Coxiella burnetii (Q fever), Brucella species (brucellosis), Burkhoderia mallei (glanders), Chlamydia psittaci (psittacosis), Rickettsia prowazekii (typhus fever), diarrheagenic E. coli , pathogenic Vibrios, Shigella species, Salmonella, Listeria monocytogenes, Campylobacter jejuni , and Yersinia enterocolitica.
181 . The method of claim 178 , wherein the one or more microorganisms are selected from Bacillus anthracis, Franciscella tularensis, Yersinia pestis, Burkholderia mallei , and Burkholderia pseudomallei.
182 . The method of claim 181 , wherein the one or more microorganisms are selected from Burkholderia mallei and Burkholderia pseudomallei.
183 . The method of claim 181 , wherein the one or more microorganisms are Burkholderia pseudomallei.
184 . The method of claim 178 , wherein the one or more microorganisms are extremely-drug resistant Gram-positive or Gram-negative pathogens.
185 . The method of any one of claims 177 - 184 , wherein the therapeutically effective amount is from about 0.1 mg to about 1500 mg.
186 . The method of claim 185 , wherein the therapeutically effective amount is about 0.5 mg, about 1 mg, about 1.5 mg, about 2.5 mg, about 5 mg, about 10 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, about 500 mg, about 525 mg, about 550 mg, about 575 mg, about 600 mg, about 625 mg, about 650 mg, about 675 mg, about 700 mg, about 725 mg, about 750 mg, about 775 mg, about 800 mg, about 825 mg, about 850 mg, about 875 mg, about 900 mg, about 925 mg, about 950 mg, about 975 mg, about 1000 mg, about 1025 mg, about 1050 mg, about 1075 mg, about 1100 mg, about 1125 mg, about 1150 mg, about 1175 mg, about 1200 mg, about 1225 mg, about 1250 mg, about 1275 mg, about 1300 mg, about 1325 mg, about 1350 mg, about 1375 mg, about 1400 mg, about 1425 mg, about 1450 mg, about 1475 mg, or about 1500 mg.
187 . The method of any one of claims 177 - 186 , wherein the compound or pharmaceutically acceptable composition is administered optically, ophthalmically, nasally, orally, parenterally, topically, or intravenously.
188 . A kit comprising a container, a compound of any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, or a pharmaceutically acceptable composition of claim 176 , and instructions for use in the treatment of a microbial infection.
189 . A kit comprising a container, a compound of any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, and instructions for use in the prevention of a microbial infection.
190 . A kit comprising a container, a compound of any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, and instructions for use in reducing the risk of a microbial infection.
191 . The kit of any one of claims 188 - 190 , wherein the microbial infection is caused by or involves one or more microorganisms which are capable of being used as biological weapons.
192 . The kit of claim 191 , wherein the one or more microorganisms are selected from the group consisting of biodefense category A pathogens Bacillus anthracis (anthrax), Yersinia pestis (plague), and Francisella tularensis (tularemia).
193 . The kit of claim 191 , wherein the one or more microorganisms are selected from the group consisting of biodefense category B pathogens Burkholderia pseudomallei (melioidosis), Coxiella burnetii (Q fever), Brucella species (brucellosis), Burkhoderia mallei (glanders), Chlamydia psittaci (psittacosis), Rickettsia prowazekii (typhus fever), diarrheagenic E. coli , pathogenic Vibrios, Shigella species, Salmonella, Listeria monocytogenes, Campylobacter jejuni , and Yersinia enterocolitica.
194 . The kit of claim 191 , wherein the one or more microorganisms are selected from Bacillus anthracis, Francisella tularensis, Yersinia pestis, Burkholderia mallei , and Burkholderia pseudomallei.
195 . The kit of claim 194 , wherein the one or more microorganisms are Burkholderia pseudomallei.
196 . Use of a compound of any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, in the manufacture of a medicament for treating, preventing, or reducing a microbial infection in a subject.
197 . Use of a compound of any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, in the manufacture of a medicament for treating, preventing, reducing the risk of, or delaying the onset of a microbial infection in a subject, wherein the infection is caused by or involves one or more microorganisms which are capable of being used as biological weapons, or the infection is caused by or involves one or more microorganisms which are extremely-drug resistant Gram-positive or Gram-negative pathogens.
198 . A compound according to any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, for use in treating, preventing, or reducing a microbial infection in a subject.
199 . The compound of any one of claims 1 - 175 , or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, for use in treating, preventing, reducing the risk of, and/or delaying the onset of a microbial infection in a subject, wherein the infection is caused by or involves one or more microorganisms which are capable of being used as biological weapons, or the infection is caused by or involves one or more microorganisms which are extremely-drug resistant Gram-positive or Gram-negative pathogens.Cited by (0)
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